Despite significant research efforts, the precise circuitry and mechanisms that causally underlie this debilitating disorder remain unclear. To fulfill the ICAMH’s commitment to alleviating the suffering caused by mental health disorders such as depression, it is crucial to understand how the brain generates depressive symptoms. My dissertation research seeks to advance current knowledge by identifying the specific neurons in discrete brain regions that trigger depressive-like episodes, while also characterizing their interactions with depression-relevant non-neuronal cells, particularly microglia. Using an advanced chemogenetic approach and a murine model of inflammation-induced depressive-like episode, I will investigate the hypothesis that activation of neuronal ensembles representing a depression-inducing stimulus (inflammatory engram neurons) within specific brain regions leads to distinct depressive-like symptoms. My specific aims are: 1. To identify and label depression-associated engram neurons. 2. To examine the behavioral consequences of stimulating engram neurons in specific brain regions associated with various depressive symptoms. 3. To investigate the effects of blocking LPS-responsive engram neurons in discrete brain regions on depressive-like symptoms. 4. To elucidate the interactions between LPS-responsive engram neurons and microglia. My Ph.D. research will be the first to comprehensively determine the precise neuronal representation of the discrete symptoms that comprise a depressive episode. These results are anticipated to be leveraged in the development of fine-tuned, individualized interventions such as targeted brain region stimulation for specific depressive symptoms in patients. Additionally, the insights gained will facilitate the development of novel pharmacological treatments that target the depression-associated disturbances in microglia-neuronal interactions.

Advisors: Prof. Raz Yirmiya and Prof. Inbal Goshen